Endometriosis Part II: Treatment

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How do we treat endometriosis? 

  • Approach 

    • Should be based on severity of symptoms and make sure that other causes of pelvic pain are excluded 

    • Usually, medications are tried first because of the risks, recovery, and costs of surgery

    • Discussion of desire for fertility in the future can also help guide your management 

    • Review with patients that this is a chronic disease - it is not curable, but can be treated. Also, discuss that the road through treatment can be long, and that one mode of therapy that is effective for some, may not be effective for others 

  • Medical 

    • NSAIDS 

      • Can be used to treat primary dysmenorrhea, and is first line for that 

      • However, no high-quality data reporting its efficacy in endometriosis; however it is low-cost and readily available; usually combined with combined hormonal therapy 

    • Estrogen-progestin contraceptives 

      • First line treatment for endometriosis because can be used long-term, well tolerated, and are relatively easy to use 

      • No formulation has demonstrated superiority

      • Both cyclic and continuous dose appear to be effective at reducing pain, but two systemic reviews reported that continuous COC regimens were more effective at reducing pain than cyclic (meaning you take the active pills in one pack → move on to the next pack, skip the placebos) 

      • This is because COCs suppress ovarian function while they are being taken and can reduce endometriosis disease activity and pain 

      • Obviously, there are risks and benefits of taking COCs, and there are many people that cannot take COCs because of the estrogen component (check out our past episode!)

    • Progestins 

      • If people can’t take estrogen, then they can use progestin only therapy 

      • Most commonly = norethindrone acetate 5 mg by mouth daily, but can be increased by 2.5 until l15 mg daily is the max

      • Depo Provera - 150 mg IM injection q12 weeks 

      • Progestins inhibit endometrial tissue growth. It also doesn’t carry the risk of VTE with COCs, and avoids risk of bone loss and menopausal symptoms associated with GnRH agonists

      • However, side effects include increased breakthrough bleeding, weight gain (Depo Provera), mood changes 

      • Alternatives: Etonogestrel implant - observational trial of 41 women showed it decreased intensity of endometriosis-related pain

      • LNG-IUD - limited evidence, but postop IUD can reduce recurrence of dysmenorrhea in women with surgically confirmed endo 

    • Gonadotropin-releasing hormone agonists 

      • I.e., leuprolide; others are things like buserelin, goserelin, etc 

      • Meta-analysis shows they are more effective than placebo, and just as effective as other medical therapies 

      • Common doses: Leuprolide 3.75 IM qmonth or 11.25 mg q3 month 

      • However, remember that it is a GnRH AGONIST 

        • Initially, can worsen symptoms for a little bit due to initial surge of LH and FSH before eventually suppressing the HPO axis (warn patients about 7-14 days of worsening symptoms) 

      • To counteract the hypoestrogenic effects (ie. menopausal symptoms, vasomotor symptoms), usually will do add-back therapy with 5 mg oral norethindrone 

    • GNRH Antagonist 

      • Also suppress HPO axis, but does so immediately, without initial LH and FSH surge like agonists 

      • Also induces a hypoestrogenic state and can cause vasomotor symptoms, as well as leads to decrease in bone density  

      • Easier to dose because they are oral rather than IM 

      • Ex: elagolix (Orilissa), dosed 150 daily up to 200 mg twice daily 

    • Danazol

      • Can be effective in reducing pain, but not common because it can cause androgenic side effects  

    • Aromatase inhibitors 

      • Usually reserved for severe, refractory endometriosis-related pain 

      • Often used in combination with progestins 

      • Off-label use of AI 

      • Limited data overall, but does seem to decrease pain compared to placebo 

      • Similarly, can cause hypoestrogenic side effects 

    • Neuropathic pain treatments 

      • Can be used if there is still pain from endometriosis (see other below)  

  • Other 

    • Often, long-lasting pain from endometriosis can become chronic pain 

    • See our chronic pain episode → basically can lead to a cycle of lowered threshold of stimulus to cause pain, central sensitization 

    • May also need other therapy such as pelvic floor PT

    • May need neuropathic pain treatments (ie. gabapentin) to decrease sensitization. Remember to remind your patients that gabapentin does not take pain away immediately, and needs to be used consistently for several weeks 

  • A note on opioids 

    • Patients with endometriosis and pelvic pain may receive opioids for pain relief when presenting for treatment urgently 

    • Opioids should be used sparingly or avoided for endometriosis and CPP because they only treat symptoms and do not address the issue 

    • Can lead to dependence and overuse 

  • Surgical 

    • There are many, many surgeries out there for endometriosis, from simple ablation, to adhesiolysis, to nerve transections, to hysterectomies. We will cover a few 

    • Surgery offers the benefit of definitive diagnosis, but risks include damage to organs (especially if there is heavy burden of endometriosis as well as adhesions) like bladder and bowel

    • Most people will achieve initially pain relief after surgery - women who underwent operative laparoscopy were 3x more likely to report improvement in pain at 12 months than controls who had diagnostic laparoscopy (one study showed 73 vs 21%) 

    • However, nearly 20% of patient will undergo repeat surgery within 2 years because of recurrent symptoms, and risk of symptom recurrence is as high as 40% at 10 year follow up 

    • Risk factors for persistent or recurrent pain: incomplete excision, ovarian cyst drainage instead of cyst excision, and ovarian conservation

    • Endometriosis tends to get better with Menopause, and so longer latency to menopause gives more time for symptoms to recur 

    • Postoperative medical therapy: ASRM advises posteropative medical suppressive therapy for most women treated surgically 

      •  6-24 months of suppression can reduce symptom recurrence and thus potentially avoid need for multiple surgeries 

      • Best evidence comes from 2 systemic reviews: one using LNG-IUD, and another for postoperative use of COCs for prevention of relapse 

  • Surgical techniques

    • Laparoscopy generally favored over laparotomy because less invasive and improves visualization, with better recovery and shorter hospital stay, elss pain 

    • Conservative 

      • Excision or ablation of endometriosis lesions with intent of preserving the uterus and as much ovarian tissue as possible 

      • First line option for most people who want surgery for endometriosis because it preserves fertility and hormone production

      • Remember: even in young patients who don’t want fertility, hormone production is necessary for bone and cardiac health!  

      • Less invasive and morbid than definitive surgery, and there is documented short term efficacy 

      • 2014 systematic review: decreased pain and increased live birth rate after conservative surgery 

      1. Disadvantages: 

        1. Rate of recurrent symptoms is higher compared to definitive surgery 

        2. Rate of reoperation increases with time, whereas it is relatively stable with definitive surgery 

    1. Hysterectomy without oophorectomy 

      1. For patients who have debilitating symptoms and whom have completed childbearing 

      2. Failed both medical therapy and at least one conservative treatment procedure 

      3. Also reasonable if other indications for a hyst (ie symptomatic fibroids, prolapse, etc) 

      4. Effective treatment for pain symptoms from endometriosis, with reoperative rates that are relatively low (19% in one study, compared to 58% in people undergoing conservative therapy) 

      5. Disadvantages 

        1. Longer, more morbid surgery with higher rates of complication 

    2. Hysterectomy with oophorectomy

      1. Those who would benefit are those with extensive adnexal disease and those for whom the risks of reoperation outweigh the risks of premature menopause 

      2. Likely increases the efficacy of definitive surgery but is accompanied by quality of life issues and potential adverse outcomes due to early menopause 

      3. Reason to do it: endometriosis is an estrogen-dependent disease, and tends to get better with menopause 

      4. Early menopause (<44 years) is associated with increase risks of overall mortality, cardiovascular disease, neurologic disease, osteoporosis